Background/Case Studies: Transfusion-Related Acute Lung Injury (TRALI) is a serious and potentially fatal complication of blood transfusion, characterized by acute hypoxemia and non-cardiogenic pulmonary edema occurring within 6 hours of transfusion. TRALI has been associated with donor-derived anti-leukocyte antibodies in 50-80% of cases; however, antibody-negative TRALI, mediated by non-immunologic mechanisms mostly related to storage time of cellular blood products, is increasingly recognized. This form poses unique diagnostic challenges, particularly in patients with complex clinical backgrounds. We present two illustrative cases of possible antibody-negative TRALI in high-risk surgical settings to highlight the importance of clinical suspicion and multidisciplinary evaluation.
Study
Design/Methods: The first patient is a 67-year-old male who underwent bilateral lung transplantation for stage 3 pulmonary hypertension. One day post-op, he received one unit of leukocyte-reduced red blood cells (LR-RBCs). One hour later, he started coughing and his SPO2 dropped to 86%. Chest X-ray showed bilateral diffuse alveolar opacities. Lung biopsy showed extensive acute lung injury consisting of abundant neutrophils in airspaces with edema and hemorrhage suggestive of a TRALI process [Figure. 1]. He was placed on ECMO until he eventually underwent a second bilateral lung transplantation.
The second patient is a 71-year-old male who underwent a planned minimally invasive mitral valve repair and Cox maze procedure. Intraoperatively, shortly after receiving two units of LR-RBCs, he developed worsening hypoxia (PaO₂ fell from 521 to 67 mmHg) and hypotension, prompting a chest x-ray that revealed new bilateral patchy infiltrates. The patient required ECMO support and intensive care.
Results/Findings: A comprehensive transfusion reaction workup was initiated in both cases. All components transfused were type-specific and crossmatch-compatible. Pre- and post-transfusion samples showed no hemolysis, and the direct antiglobulin test was negative. Given the temporal relationship to transfusion, acute non-cardiogenic respiratory deterioration, and radiologic findings in both cases, TRALI was deemed a probable diagnosis.
The blood products’ supplier was informed. The donors in both cases are deemed not at risk of developing anti-leukocyte antibodies and have never been implicated in previous TRALI reactions. However, given the severity of symptoms of the first case, specimens from both the donor and recipient were tested and found negative for anti-leukocyte antibodies.
Conclusions: These cases emphasize the importance of recognizing antibody-negative TRALI as a distinct clinical entity, particularly in complex surgical settings where differential diagnoses are broad. Increased awareness can facilitate timely diagnosis and improve patient outcomes in high-risk transfusion scenarios such as lung transplantation and cardiac surgery.
